Structural basis for assembly of lamin at the molecular level

Nuclear structure and function are governed by lamins, which are intermediate filaments mostly consisting of alpha-helices. Different lamin assembly models have been proposed based on low resolution or fragmented structures. However, their assembly mechanisms at the molecular level are poorly understood. Here, we present a crystal structure of a long human lamin fragment at 3.2 Å resolution, which visualized the full-length features. The structure presented the anti-parallel arrangement of two coiled-coil dimers, which was important for the assembly process. We further discovered a new interaction between the lamin dimers by using chemical cross-linking and mass analysis. Based on these two interactions we proposed a molecular mechanism of lamin assembly, which agreed well with the recent model representing the native state, and could explain pathological mutations. Our findings provide the structural information to understand molecular mechanisms of assembly of intermediate filaments, and molecular insights into nuclear functions and aging process.